An international view of hydroxyethyl starches

Hydroxyethyl starch (HES) is one of the most frequently used plasma substit utes. A variety of different HES solutions exist worldwide, which differ gr eatly in their pharmacological properties. HES is classified according to i ts manufactured or in vitro molecular weight (MW) into high MW (450-480 kDa ), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, t his is not sufficient, because as HES is metabolized in vivo, its MW change s, and it is the in vivo MW which is responsible for the therapeutic and ad verse effects, of each HES. The rate of metabolization depends mainly on th e degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2 /C6 ratio of hydroxyethylation. A high degree of substitution and a high C2 /C6 ratio lead to a slow metabolization of HES, resulting in a large in viv o MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a hig h in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect, When infusing higher volumes (> 1500 mi) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin cl ots, and an unfavorable effect on rheological parameters. Rapidly degradabl e medium MW HES 200/05 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal eliminati on, shorter volume effect, and fewer adverse effects on coagulation and rhe ological parameters. For historical and marketing reasons, only slowly degradable, high MW HES ( 480/0.7) is available in the United States. In Europe, a large variety of H ES solutions are available, dominated by medium MW, easily degradable HES ( 200/0.5). Because of increasing international competition and the availabil ity of newly developed starches, it is important to be aware of the pharmac ological properties of HES and the advantages and disadvantages of the indi vidual preparations.